LIBERATE Trial in COVID-19 (LIBERATE)

Lipid Ibuprofen Versus Standard of Care for Acute Hypoxemic Respiratory Failure Due to COVID-19: a Multicentre, Randomised, Controlled Trial

The study aims to evaluate the reduction in severity and progression of lung injury with three doses of lipid ibuprofen in patients with SARS-CoV-2 infections.

Study Overview

• Status: Withdrawn
• Conditions: Respiratory Distress Syndrome; SARS-CoV Infection; Coronavirus
• Intervention / Treatment: Drug: Ibuprofen

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • Guy's and St Thomas' NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female patients aged 18 years and above;
2. Hospitalised;
3. Confirmed or suspected SARS-CoV-2 infection;
4. National Early Warning Score (NEWS2) greater than or equal to 3 in a single parameter or NEWS2 > 5 overall;
5. Acute hypoxemic respiratory failure: PaO2/FiO2 ratio less than or equal to 300 OR SpO2/FiO2 ratio < 315 (Kigali Modification)
6. Provision of written informed consent by the patient OR by the patient's Legal Representative OR professional consultee.

Exclusion Criteria:

1. Any of the following contraindications to ibuprofen:

   • A known hypersensitivity to ibuprofen or any other constituent of the medicinal product;
   • Patients who have previously shown hypersensitivity reactions (e.g. asthma, rhinitis, angioedema or urticaria) in response to aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs);
   • Patients with a history of, or existing gastrointestinal ulceration/perforation or bleeding, including that associated with NSAIDs;
   • Patients with severe hepatic failure;
   • Patients with acute renal failure;
   • Patients with severe heart failure.
2. Participation in any other investigational drug products less than 30 days prior to study enrolment;
3. Glasgow Coma Score < 12;
4. Patients who cannot swallow oral capsules;
5. Pregnant or lactating women;
6. Any medical history that might, in the opinion of the attending clinician, put the patient at significant risk if he/she were to participate in the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard of care
Experimental: Standard of care plus lipid ibuprofen	Drug: Ibuprofen; Lipid ibuprofen 200 mg; Other Names: Flarin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease progression	Worsening respiratory failure; defined using severity of hypoxaemia using [PaO2/FiO2 ratio OR SpO2/FiO2 ratio]	14 days
Time to mechanical ventilation	Time to mechanical ventilation (or need of)	14 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival	28 days
Reduction in proportion of patients who require ventilation	28 days
Reduction in length of Critical Care stay	28 days
Reduction in length of Hospital stay	28 days
Modulation of serum pro- and anti-inflammatory cytokines	28 days
Reduction in duration of ventilation	28 days
Increase in ventilator-free days	28 days

Collaborators and Investigators

• Sponsor: King's College London
• Collaborators: Guy's & St Thomas NHS Foundation Trust
• Investigators: Principal Investigator: Richard Beale, MD, Guy's and St Thomas' NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): May 26, 2020
• Primary Completion (Actual): May 25, 2021
• Study Completion (Actual): September 25, 2021

Study Registration Dates

• First Submitted: April 2, 2020
• First Submitted That Met QC Criteria: April 2, 2020
• First Posted (Actual): April 6, 2020

Study Record Updates

• Last Update Posted (Actual): July 25, 2023
• Last Update Submitted That Met QC Criteria: July 24, 2023
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Infant, Newborn, Diseases; Infant, Premature, Diseases; Severe Acute Respiratory Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Ibuprofen
• Other Study ID Numbers: 282009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No